Nivolumab and interferon-γ rescue therapy to control mixed mould and bacterial superinfection after necrotizing fasciitis and septic shock

Lukaszewicz, Anne‐Claire; Venet, Fabienne; Boibieux, A.; Lherm, Mathilde; Dévigne, Bertrand; Monneret, Guillaume

doi:10.1016/j.mmcr.2022.06.003

Cited by 12 publications

(10 citation statements)

References 11 publications

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“… 3) Combination therapy: combination therapy with G-CSF and GM-CSF may be used as was done in the present case. Combined therapy of IFN-γ and anti-PD-1 has been reported ( 9 , 15 ). …”

Section: Discussionmentioning

confidence: 99%

Immune Adjuvant Therapy With Interleukin-7 in a Lymphopenic Patient With Aplastic Anemia and Mucormycosis

Crees,

Patel,

Dram

et al. 2023

Critical Care Explorations

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BACKGROUND: We report the case of a patient with aplastic anemia and pancytopenia on immune-suppressive therapy who developed invasive pulmonary infection with mucormycosis and was treated with immune adjuvant therapy. CASE SUMMARY: Given the patient’s profound lymphopenia and progressive invasive mucor despite dual antifungal drug therapy, interleukin (IL)-7, a cytokine that induces lymphocyte activation and proliferation, was instituted and resulted in normalization of absolute lymphocyte counts and was temporally associated with clearance of fungal pathogens and resolution of clinical symptoms. CONCLUSION: Patients with life-threatening fungal infections are frequently immune suppressed and immune adjuvant therapies should be considered in patients who are not responding to antifungal drugs and source control. Well-designed, double-blind, placebo-controlled trials are needed to advance the field. Although a number of immune adjuvants may be beneficial in fungal sepsis, IL-7 is a particularly attractive immune adjuvant because of its broad immunologic effects on key immunologic pathways that mediate enhanced antifungal immune system activity.

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“… 3) Combination therapy: combination therapy with G-CSF and GM-CSF may be used as was done in the present case. Combined therapy of IFN-γ and anti-PD-1 has been reported ( 9 , 15 ). …”

Section: Discussionmentioning

confidence: 99%

Immune Adjuvant Therapy With Interleukin-7 in a Lymphopenic Patient With Aplastic Anemia and Mucormycosis

Crees,

Patel,

Dram

et al. 2023

Critical Care Explorations

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“…In preclinical work and in a limited number of case reports or case series in IA, beneficial results have been seen with recombinant interferon-gamma (rIFNc), which increases phagocytic antifungal activity, and checkpoint-inhibitors (e.g. anti-PD-1), which counter immune cell exhaustion [104][105][106][107][108][109][110][111][112][113][114][115][116][117]. The potential of rIFN-c has been investigated more thoroughly in the setting of prevention of IA in patients with chronic granulomatous disease specifically, and in chronic pulmonary aspergillosis [118,119].…”

Section: Immunotherapymentioning

confidence: 99%

Treatment of Invasive Aspergillosis: How It’s Going, Where It’s Heading

et al. 2023

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Despite improvements in treatment and diagnostics over the last two decades, invasive aspergillosis (IA) remains a devastating fungal disease. The number of immunocompromised patients and hence vulnerable hosts increases, which is paralleled by the emergence of a rise in IA cases. Increased frequencies of azole-resistant strains are reported from six continents, presenting a new challenge for the therapeutic management. Treatment options for IA currently consist of three classes of antifungals (azoles, polyenes, echinocandins) with distinctive advantages and shortcomings. Especially in settings of difficult to treat IA, comprising drug tolerance/resistance, limiting drug–drug interactions, and/or severe underlying organ dysfunction, novel approaches are urgently needed. Promising new drugs for the treatment of IA are in late-stage clinical development, including olorofim (a dihydroorotate dehydrogenase inhibitor), fosmanogepix (a Gwt1 enzyme inhibitor), ibrexafungerp (a triterpenoid), opelconazole (an azole optimized for inhalation) and rezafungin (an echinocandin with long half-life time). Further, new insights in the pathophysiology of IA yielding immunotherapy as a potential add-on therapy. Current investigations show encouraging results, so far mostly in preclinical settings. In this review we discuss current treatment strategies, give an outlook on possible new pharmaceutical therapeutic options, and, lastly, provide an overview of the ongoing research in immunotherapy for IA.

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“…In another recent case report ( 54 ), combined immunotherapy with nivolumab and IFN-γ was used to treat an extensive polymicrobial soft tissue infection secondary to a minor thoracic trauma in a previously healthy 38-year-old female patient. Pathogens identified by culture and molecular techniques included Enterococci , multiple gram-negative bacteria, Aspergillus spp., Mucor spp., L. ramosa , and Rhizopus arrhizus .…”

Section: The Growing Promise Of Icis In Medical Mycologymentioning

confidence: 99%

“…PD-1 expression became negative on the following day, fungal cultures and PCR became negative over the course of one week, and the patient’s clinical status improved rapidly. The patient was discharged after 5.5 months following extensive reconstructive surgery ( 54 ).…”

Section: The Growing Promise Of Icis In Medical Mycologymentioning

confidence: 99%

Checkpoint inhibitors as immunotherapy for fungal infections: Promises, challenges, and unanswered questions

2022

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Opportunistic fungal infections have high mortality in patients with severe immune dysfunction. Growing evidence suggests that the immune environment of invasive fungal infections and cancers share common features of immune cell exhaustion through activation of immune checkpoint pathways. This observation gave rise to several preclinical studies and clinical case reports describing blockade of the Programmed Cell Death Protein 1 and Cytotoxic T-Lymphocyte Antigen 4 immune checkpoint pathways as an adjunct immune enhancement strategy to treat opportunistic fungal infections. The first part of this review summarizes the emerging evidence for contributions of checkpoint pathways to the immunopathology of fungal sepsis, opportunistic mold infections, and dimorphic fungal infections. We then review the potential merits of immune checkpoint inhibitors (ICIs) as an antifungal immunotherapy, including the incomplete knowledge of the mechanisms involved in both immuno-protective effects and toxicities. In the second part of this review, we discuss the limitations of the current evidence and the many unknowns about ICIs as an antifungal immune enhancement strategy. Based on these gaps of knowledge and lessons learned from cancer immunology studies, we outline a research agenda to determine a “sweet spot” for ICIs in medical mycology. We specifically discuss the importance of more nuanced animal models, the need to study ICI-based combination therapy, potential ICI resistance, the role of the immune microenvironment, and the impact of ICIs given as part of oncological therapies on the natural immunity to various pathogenic fungi.

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Nivolumab and interferon-γ rescue therapy to control mixed mould and bacterial superinfection after necrotizing fasciitis and septic shock

Cited by 12 publications

References 11 publications

Immune Adjuvant Therapy With Interleukin-7 in a Lymphopenic Patient With Aplastic Anemia and Mucormycosis

Immune Adjuvant Therapy With Interleukin-7 in a Lymphopenic Patient With Aplastic Anemia and Mucormycosis

Treatment of Invasive Aspergillosis: How It’s Going, Where It’s Heading

Checkpoint inhibitors as immunotherapy for fungal infections: Promises, challenges, and unanswered questions

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